Limits...
Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology.

Lensen JF, van der Vlag J, Versteeg EM, Wetzels JF, van den Heuvel LP, Berden JH, van Kuppevelt TH, Rops AL - PLoS ONE (2015)

Bottom Line: Expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 was decreased in the interstitium of transplant kidneys with IF/TA, which was accompanied by an increased expression of type I collagen, decorin and transforming growth factor beta (TGF-β), while its expression was increased in the interstitium in FSGS, MGP and SLE.Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients.Further research is required to delineate the exact role of different DS domains in renal fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

ABSTRACT
Dermatan sulfate (DS), also known as chondroitin sulfate (CS)-B, is a member of the linear polysaccharides called glycosaminoglycans (GAGs). The expression of CS/DS and DS proteoglycans is increased in several fibrotic renal diseases, including interstitial fibrosis, diabetic nephropathy, mesangial sclerosis and nephrosclerosis. Little, however, is known about structural alterations in DS in renal diseases. The aim of this study was to evaluate the renal expression of two different DS domains in renal transplant rejection and glomerular pathologies. DS expression was evaluated in normal renal tissue and in kidney biopsies obtained from patients with acute interstitial or vascular renal allograft rejection, patients with interstitial fibrosis and tubular atrophy (IF/TA), and from patients with focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy (MGP) or systemic lupus erythematosus (SLE), using our unique specific anti-DS antibodies LKN1 and GD3A12. Expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 was decreased in the interstitium of transplant kidneys with IF/TA, which was accompanied by an increased expression of type I collagen, decorin and transforming growth factor beta (TGF-β), while its expression was increased in the interstitium in FSGS, MGP and SLE. Importantly, all patients showed glomerular LKN1 staining in contrast to the controls. Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients. Our data suggest a role for the DS domain recognized by antibody LKN1 in renal diseases with early fibrosis. Further research is required to delineate the exact role of different DS domains in renal fibrosis.

No MeSH data available.


Related in: MedlinePlus

Correlation between the expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 and type I collagen (A) and the expression ratio of LKN1 and GD3A12 (B) in glomerular diseases, acute rejection and IF/TA.In acute (vascular and interstitial) rejection, the interstitial expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 is increased, while expression of collagen type I is decreased (A). Expression of collagen type I is increased in glomerular diseases and IF/TA, which is accompanied by an increased expression of the 4/2,4-di-O-sulfated DS domain in glomerular diseases and a decreased expression of the 4/2,4-di-O-sulfated DS domain in IF/TA. The expression ratio of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 to the IdoA-Gal-NAc4S DS domain recognized by antibody GD3A12 is decreased in the IF/TA patients in contrast to the patients with acute rejection or glomerular diseases (B).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556443&req=5

pone.0134946.g005: Correlation between the expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 and type I collagen (A) and the expression ratio of LKN1 and GD3A12 (B) in glomerular diseases, acute rejection and IF/TA.In acute (vascular and interstitial) rejection, the interstitial expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 is increased, while expression of collagen type I is decreased (A). Expression of collagen type I is increased in glomerular diseases and IF/TA, which is accompanied by an increased expression of the 4/2,4-di-O-sulfated DS domain in glomerular diseases and a decreased expression of the 4/2,4-di-O-sulfated DS domain in IF/TA. The expression ratio of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 to the IdoA-Gal-NAc4S DS domain recognized by antibody GD3A12 is decreased in the IF/TA patients in contrast to the patients with acute rejection or glomerular diseases (B).

Mentions: In summary, we observed a differential expression of the 4/2,4-di-O-sulfated DS domain, recognized by antibody LKN1, in renal transplant rejection and glomerular pathologies. We analyzed the correlation between the expression of 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 and type I collagen in glomerular diseases, acute rejection and IF/TA, which may clarify the difference of LKN1 staining in the different renal diseases (Fig 5A). We observed 3 patterns; 1) in acute allograft rejection expression of the 4/2,4-di-O-sulfated DS domain recognized by LKN1 is increased more than collagen type I; 2) in glomerular disease both expressions are increased; 3) but in IF/TA expression of the 4/2,4-di-O-sulfated DS domain is decreased, while collagen type I is increased. In contrast to the differential interstitial expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 among the various renal diseases, the expression of the IdoA-Gal-NAc4S DS domain recognized by GD3A12 is similar in healthy and diseased kidneys. Therefore, the expression ratio of 4/2,4-di-O-sulfated DS domain to IdoA-Gal-NAc4S DS domain might be useful in monitoring the progression of IF/TA (Fig 5B). This information may be useful for diagnostic purposes on renal biopsies.


Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology.

Lensen JF, van der Vlag J, Versteeg EM, Wetzels JF, van den Heuvel LP, Berden JH, van Kuppevelt TH, Rops AL - PLoS ONE (2015)

Correlation between the expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 and type I collagen (A) and the expression ratio of LKN1 and GD3A12 (B) in glomerular diseases, acute rejection and IF/TA.In acute (vascular and interstitial) rejection, the interstitial expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 is increased, while expression of collagen type I is decreased (A). Expression of collagen type I is increased in glomerular diseases and IF/TA, which is accompanied by an increased expression of the 4/2,4-di-O-sulfated DS domain in glomerular diseases and a decreased expression of the 4/2,4-di-O-sulfated DS domain in IF/TA. The expression ratio of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 to the IdoA-Gal-NAc4S DS domain recognized by antibody GD3A12 is decreased in the IF/TA patients in contrast to the patients with acute rejection or glomerular diseases (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556443&req=5

pone.0134946.g005: Correlation between the expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 and type I collagen (A) and the expression ratio of LKN1 and GD3A12 (B) in glomerular diseases, acute rejection and IF/TA.In acute (vascular and interstitial) rejection, the interstitial expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 is increased, while expression of collagen type I is decreased (A). Expression of collagen type I is increased in glomerular diseases and IF/TA, which is accompanied by an increased expression of the 4/2,4-di-O-sulfated DS domain in glomerular diseases and a decreased expression of the 4/2,4-di-O-sulfated DS domain in IF/TA. The expression ratio of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 to the IdoA-Gal-NAc4S DS domain recognized by antibody GD3A12 is decreased in the IF/TA patients in contrast to the patients with acute rejection or glomerular diseases (B).
Mentions: In summary, we observed a differential expression of the 4/2,4-di-O-sulfated DS domain, recognized by antibody LKN1, in renal transplant rejection and glomerular pathologies. We analyzed the correlation between the expression of 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 and type I collagen in glomerular diseases, acute rejection and IF/TA, which may clarify the difference of LKN1 staining in the different renal diseases (Fig 5A). We observed 3 patterns; 1) in acute allograft rejection expression of the 4/2,4-di-O-sulfated DS domain recognized by LKN1 is increased more than collagen type I; 2) in glomerular disease both expressions are increased; 3) but in IF/TA expression of the 4/2,4-di-O-sulfated DS domain is decreased, while collagen type I is increased. In contrast to the differential interstitial expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 among the various renal diseases, the expression of the IdoA-Gal-NAc4S DS domain recognized by GD3A12 is similar in healthy and diseased kidneys. Therefore, the expression ratio of 4/2,4-di-O-sulfated DS domain to IdoA-Gal-NAc4S DS domain might be useful in monitoring the progression of IF/TA (Fig 5B). This information may be useful for diagnostic purposes on renal biopsies.

Bottom Line: Expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 was decreased in the interstitium of transplant kidneys with IF/TA, which was accompanied by an increased expression of type I collagen, decorin and transforming growth factor beta (TGF-β), while its expression was increased in the interstitium in FSGS, MGP and SLE.Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients.Further research is required to delineate the exact role of different DS domains in renal fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

ABSTRACT
Dermatan sulfate (DS), also known as chondroitin sulfate (CS)-B, is a member of the linear polysaccharides called glycosaminoglycans (GAGs). The expression of CS/DS and DS proteoglycans is increased in several fibrotic renal diseases, including interstitial fibrosis, diabetic nephropathy, mesangial sclerosis and nephrosclerosis. Little, however, is known about structural alterations in DS in renal diseases. The aim of this study was to evaluate the renal expression of two different DS domains in renal transplant rejection and glomerular pathologies. DS expression was evaluated in normal renal tissue and in kidney biopsies obtained from patients with acute interstitial or vascular renal allograft rejection, patients with interstitial fibrosis and tubular atrophy (IF/TA), and from patients with focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy (MGP) or systemic lupus erythematosus (SLE), using our unique specific anti-DS antibodies LKN1 and GD3A12. Expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 was decreased in the interstitium of transplant kidneys with IF/TA, which was accompanied by an increased expression of type I collagen, decorin and transforming growth factor beta (TGF-β), while its expression was increased in the interstitium in FSGS, MGP and SLE. Importantly, all patients showed glomerular LKN1 staining in contrast to the controls. Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients. Our data suggest a role for the DS domain recognized by antibody LKN1 in renal diseases with early fibrosis. Further research is required to delineate the exact role of different DS domains in renal fibrosis.

No MeSH data available.


Related in: MedlinePlus